Michael Fox

An AJP commentary puts forth that lithium is vastly underutilized in the treatment of bipolar disorder, with its large array of assets underestimated and its side effects overemphasized. bit.ly/4dtCOqe

Little evidence that cannabis products are effective treatments for mental health conditions, finds largest study to date. Explore the research in The Lancet Psychiatry 👉 spkl.io/6019ALn1U

A new approach, called temporal interference stimulation, offers access to deep-brain areas previously only targetable with surgery. scim.ag/3NLecij

A more visual summary of our recent paper and why the 'know-cebo' effect matters

Damage to the amygdala is associated with reduced empathic accuracy. However, Scheffer et al. show that patients with amygdala lesions are as motivated to empathise as controls, indicating that motivational components of empathy are preserved. shorturl.at/QgvdF

🚨MAJOR NEW PAPER 🚨 just out in @JAMAPsych : Psychedelic Therapy vs Antidepressants for the Treatment of Depression Under Equal Unblinding Conditions (tinyurl.com/yu2rbtaf). I am very proud of this one, was a lot of work for me - both co-first and last author! Eternal gratitude to co-first @QuantPsychiatry and twitterless Hannah Barnett! The premise is that it is biased to compare open-label trials (=where patients know what treatment they are getting) to blind trials (=where patients do NOT know what they are getting). Open-label trials would gain an unfair advantage by higher placebo response. Even formally blinded psychedelic trials are practically open-label as its obvious to distinguish placebo from 25mg of #psilocybin. In contrast, traditional antidepressants (SSRIs/SNRIs) trials are are close to be truly blind (Lin 2022). Given the bias of open-label vs. blinded comparison, we compared the efficacy of psychedelic-therapy (which is practically always open-label) vs. open-label antidepressants for the treatment of major depression. We tested 3 prior hypothesis: - There will be a significant difference between psychedelic-therapy vs. open-label antidepressants, favoring psychedelic-therapy. - There will be a significant difference between blinded and open-label antidepressants trials, favoring open-label. - There will NOT be a significant difference between blinded and open-label psychedelic-therapy, as practically they are always open-label. In contrast with our prior hypothesis, we did not find psychedelic-therapy to be more effective than open-label antidepressants (H1). Not only was the difference not clinically meaningful, but practically there was no difference at all. This finding means that antidepressants administered knowingly to patients, which is the case in real-life medical practice, is as effective as psychedelic-therapy. This result was robust across variations in study selection, including when we removed psychedelic-therapy trials on treatment-resistant depression. We also assessed the impact of blinding in both psychedelic-therapy and antidepressants trials. We found that for antidepressants (H2), but not for psychedelic-therapy (H3), open label is associated with better outcomes than blinded treatment. However, even in the case of antidepressants, the difference was practically small (~1.3 HAMD units). How come hypothesis 1 failed, i.e. that psychedelic-therapy is no ore effective than open-label antidepressants, given that antidepressants trials are famous for small drug-placebo difference (~2.4 HAMD units), while psychedelic-therapy trials reported large effects (~7.3)? The key factor is that in psychedelic trials the placebo response is about 50% relative to antidepressants, ~ 4 vs 8 HAMD units (Hsu 2024, Hieronymus 2025). This suppressed placebo response leads to an inflated between-arm difference, as the treatment arm is measured against a lower floor. The suppressed placebo response in psychedelic-therapy trials is likely attributable to the ‘know-cebo’ effect, i.e. the disappointment when patients realize they are in the control group. In psychedelic-therapy trials, this placebo suppression accounts for 4.0 / 7.3 ~ 55% of the specific treatment effect. In other words, ~55% of psychedelic-therapy’s effect is not explained by patient improvement after the treatment, but rather by the lack of improvement in the placebo group. In summary, we found that for the treatment of depression, psychedelic-therapy is no more effective than open-label SSRIs/SNRIs. Our results for psychedelics are twofold: psychedelic-therapy demonstrated a robust and large therapeutic effects (~12 HAMD units), which justifies optimism. On the other hand, psychedelic-therapy’s lack of superiority compared to open-label SSRIs/SNRIs highlights the influence of blinding integrity and argues against overly optimistic narrative's about psychedelic-therapy's potential.

From neural circuits to dinner circuits - the Program Scientists are celebrating hard work (and St Patrick's Day) in Boston with the Mass Brigham team!

🧠BD²'s third annual Investigators Meeting brought together 150 researchers, clinicians & stakeholders around one theme: "Accelerating Research to Care." Through collaboration, we are turning discovery into improvements in care for people with bipolar disorder with breakthroughs in genetic pathways, neuroimaging advances, sleep-circuit insights & whole-body health models.

Thrilled to announce our new paper in @NatureNeuro ! We managed the impossible: precision functional mapping during #DBS, with 11.7h fMRI/patient. Selective DBS-induced deactivations in the SCAN, building on our recent @Nature paper. @hesheng3 @iamzhangvv nature.com/articles/s4159…

@DrPhilipMosley Not sure I can live up to that comparison, but honored to try and follow his example.

@foxmdphd a Charcot for the modern age!

Excited for the start of @anpadirect meeting today in Providence - make sure to stop by Julian Kutsche's poster this evening on visual imagery and #aphantasia

Honored to work with these pioneers of functional neurosurgery @Brain_Circuits @MGBneurosurgery who are developing new treatments for patients with Parkinson’s disease.

A milestone for Parkinson’s care in New England. Dr. Rees Cosgrove and Dr. John Rolston recently completed the region’s first case using the newly approved PTT target therapy, expanding treatment options for patients by addressing a broader range of Parkinson’s symptoms. This innovative approach reflects our continued commitment to advancing neurosurgical care and bringing the latest therapies to patients. #parkinsonstreatment #PTTtarget #FunctionalNeurosurgery

📢 Can noninvasive TMS reach & modulate the human hippocampus? 🧠⚡🧲 Multimodal evidence (TMS-iEEG + TMS-fMRI) from our new @NatureComms paper says YES: shorturl.at/fqtYR Here’s what we did and why it matters. 👇 #TMS #iEEG #fMRI #Hippocampus #Memory #Emotion

What’s the difference between a neurological vs psychiatric disorder? @Brain_Circuits, it’s only the circuit impacted. Honored to become one of the first full Professors of both Psychiatry and Neurology @harvardmed. Excited to help bridge this divide.

Can #MachineLearning program #DBS as well as neurologists in #ParkinsonsDisease? In our prospective blinded trial, ML using a single-session fMRI predicted optimal DBS contacts with outcomes non-inferior to expert clinical programming. Our newest paper in @brainstimj sciencedirect.com/science/articl… @BrendanSantyr @DrAlfonsoFasano @JurgenGermann @kalialabs @mhodaie @StefanLang_MD @UofTNeuroSurge

trying to reach the hippocampus with TMS? check out nature.com/articles/s4146…

Japan just approved stem cells for Parkinson’s disease. How will it work? Stem cells are special cells that can develop into other types of cells. In this case they are turned into dopamine-producing brain cells designed to replace the cells lost in Parkinson’s disease. Sawamoto and colleagues described in a new paper in Nature one of the first phase I/II clinical trial using induced pluripotent stem cell derived dopaminergic progenitor cells transplanted into the brains of folks living w/ Parkinson’s disease. These cells are generated from iPS cells and implanted into the putamen where dopamine neurons normally function. Key Points: - Seven folks w/ Parkinson’s disease received bilateral transplantation of dopaminergic progenitor cells derived from iPS cells into the putamen and were followed for 24 months. - The transplanted cells survived, produced dopamine, and imaging revealed a roughly 44 percent increase in dopamine related activity in the putamen. - The procedure appeared safe w/ no tumors or graft overgrowth and several participants experienced improvements in motor scores on Parkinson’s rating scales. My take: Japan has a unique regulatory pathway for regenerative medicine that allows conditional approval once safety and early signals of benefit are demonstrated. For the therapy to advance in Japan data will be collected over the next 7 years. This paper represents an important milestone because it shows that lab grown dopamine cells can survive in the human brain and begin producing dopamine. The big questions ahead will be durability, patient selection, and whether the next 7 years of experience will confirm meaningful and sustained clinical benefit. Here are 5 points that resonated w/ me: 1- Parkinson’s disease is caused by the loss of dopamine producing neurons and this therapy attempts to replace those missing cells. 2- The transplanted cells are generated from induced pluripotent stem cells which are adult cells reprogrammed to behave like embryonic stem cells. 3- Brain imaging revealed new dopamine activity in the transplanted region suggesting the cells were functioning. 4- Safety remains the first hurdle and this trial showed no tumors or uncontrolled cell growth over two years of follow up. 5- The future will likely combine cell therapy w/ medications, rehabilitation, and possibly gene therapy to maximize benefit for folks living w/ Parkinson’s disease. Here is the Nature paper that set the stage for the recent approval. nature.com/articles/s4158… #parkinson @ParkinsonDotOrg @FixelInstitute

Warm congratulations to The Brain Prize winners 2026, Professor David Ginty and Professor Patrik Ernfors, for their pioneering work on how the nervous system detects and processes touch and pain. @hhmi_science #Neuroscience #BrainPrize2026

A new systematic review of LLMs in medicine @NatureMedicine @ekoermann nature.com/articles/s4159… “Despite thousands [4,609] of publications since late 2022, only a small fraction use real clinical data and just 19 randomized trials exist.”